Differential Regulation of the Expression of the Two Thyrotropin Beta Subunit Paralogs by Salmon Pituitary Cells In Vitro

We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon, tsh beta a and tsh beta b, issued from teleost-specific whole genome duplication. The transcript expression of tsh beta b, but not of tsh beta a, peaks at the time of smoltification, which revealed a specific involvement of tsh beta b paralog in this metamorphic event. Tsh beta a and tsh beta b are expressed by distinct pituitary cells in salmon, likely related to TSH cells from the pars distalis and pars tuberalis, respectively, in mammals and birds. The present study aimed at investigating the neuroendocrine and endocrine factors potentially involved in the differential regulation of tsh beta a and tsh beta b paralogs, using primary cultures of Atlantic salmon pituitary cells. The effects of various neurohormones and endocrine factors potentially involved in the control of development, growth, and metabolism were tested. Transcript levels of tsh beta a and tsh beta b were measured by qPCR, as well as those of growth hormone (gh), for comparison and validation. Corticotropin-releasing hormone (CRH) stimulated tsh beta a transcript levels in agreement with its potential role in the thyrotropic axis in teleosts, but had no effect on tsh beta b paralog, while it also stimulated gh transcript levels. Thyrotropin-releasing hormone (TRH) had no effect on neither tsh beta paralogs nor gh. Somatostatin (SRIH) had no effects on both tsh beta paralogs, while it exerted a canonical inhibitory effect on gh transcript levels. Thyroid hormones [triiodothyronine (T3) and thyroxine (T4)] inhibited transcript levels of both tsh beta paralogs, as well as gh, but with a much stronger effect on tsh beta a than on tsh beta b and gh. Conversely, cortisol had a stronger inhibitory effect on tsh beta b than tsh beta a, while no effect on gh. Remarkably, insulin-like growth factor 1 (IGF1) dose-dependently stimulated tsh beta b transcript levels, while it had no effect on tsh beta a, and a classical inhibitory effect on gh. This study provides the first data on the neuroendocrine factors involved in the differential regulation of the expression of the two tsh beta paralogs. It suggests that IGF1 may be involved in triggering the expression peak of the tsh beta b paralog at smoltification, thus representing a potential internal signal in the link between body growth and smoltification metamorphosis.